The Dct−/− Mouse Model to Unravel Retinogenesis Misregulation in Patients with Albinism

Abstract

We have recently identified DCT encoding dopachrome tautomerase (DCT) as the eighth gene for oculocutaneous albinism (OCA). Patients with loss of function of DCT suffer from eye hypopigmentation and retinal dystrophy. Here we investigate the eye phenotype in Dct−/− mice. We show that their retinal pigmented epithelium (RPE) is severely hypopigmented from early stages, contrasting with the darker melanocytic tissues. Multimodal imaging reveals specific RPE cellular defects. Melanosomes are fewer with correct subcellular localization but disrupted melanization. RPE cell size is globally increased and heterogeneous. P-cadherin labeling of Dct−/− newborn RPE reveals a defect in adherens junctions similar to what has been described in tyrosinase-deficient Tyrc/c embryos. The first intermediate of melanin biosynthesis, dihydroxyphenylalanine (L-Dopa), which is thought to control retinogenesis, is detected in substantial yet significantly reduced amounts in Dct−/− postnatal mouse eyecups. L-Dopa synthesis in the RPE alone remains to be evaluated during the critical period of retinogenesis. The Dct−/− mouse should prove useful in understanding the molecular regulation of retinal development and aging of the hypopigmented eye. This may guide therapeutic strategies to prevent vision deficits in patients with albinism.

Investigating the impact of pigmentation variation of breast muscle on growth traits, melanin deposition, and gene expression in Xuefeng black-bone chickens

“…Mutations in TYRP1 usually can result in oculocutaneous albinism type 3 with rufous or brown phenotype in skin, hair and irises ( Patel et al, 2021 ). And recently studies defined DCT as a disease-causing gene in oculocutaneous albinism type 8 ( Tingaud-Sequeira et al, 2022 ). No candidate genes related to melanin transport were found in this study, but there are lots of studies proved all of the above genes play necessary roles in the process of melanin production in animals ( Bovo et al, 2023 ; Cheng et al, 2023 ; Li et al, 2023 ).…”

A Slc38a8 Mouse Model of FHONDA Syndrome Faithfully Recapitulates the Visual Deficits of Albinism Without Pigmentation Defects

“…More recently, mouse models have also contributed to our understanding of the retinal alterations seen in the latest type of albinism, OCA8, caused by mutations in the DCT gene. 24 , 25 However, no animal model has been made available for investigating FHONDA, apart from some morpholino knockdown experiments conducted in Medaka fish. They targeted both SLC38A8 orthologues in the fish, resulting in microphthalmia, lens defects, and fissure coloboma, with varying penetrance, and without any pigmentation defects, as in patients with FHONDA.…”

A slc38a8 mouse model of FHONDA syndrome faithfully recapitulates the visual deficits of albinism without pigmentation defects

“…23 More recently, mouse models have also contributed to our understanding of the retinal alterations seen in the latest type of albinism, OCA8, caused by mutations in the DCT gene. 24,25 However, no animal model has been made available for investigating FHONDA, apart from some morpholino knockdown experiments conducted in Medaka fish. They targeted both SLC38A8 orthologues in the fish, resulting in microphthalmia, lens defects, and fissure coloboma, with varying penetrance, and without any pigmentation defects, as in patients with FHONDA.…”